Differential expression of aristaless-like homeobox 4: a potential marker for gastric adenocarcinoma

The objective of this experiment was to evaluate the ALX-4 mRNA expression level in different stages of human gastric adenocarcinoma compared to the gastric cancer stem cells (GCSC) and gastric cancer cell line, MKN-45.

Gastric cancer is the second most common cancer in the world today, leading approximately to 3-10% of all cancer-related deaths. Identification of specific biomarkers could be a crucial approach to improve diagnosis and treatment of this cancer type. Recent findings emphasized on the up-regulation of Aristaless-Like Homeobox 4 (ALX-4) gene expression in several tumors.

MKN-45 cell culture was prepared, and gastric cancer stem cell (GCSC) isolation was performed by flowcytometry. Then, 37 fresh gastric tissue samples from cancer patient were subjected for expression analysis by quantitative RT-PCR, prior to any therapeutic intervention in the comparative study for evaluation of ALX-4 gene expression.

GCSCs with cuboidal shape as well as a positive expression of CD105, CD44, CD90 and negative for CD45, CD34 markers were identified. Overexpression of ALX-4 was detected in 46% (3.351±2.94, P<0.05) of gastric cancer tissue specimens and GCSCs (4.31±0.04, P<0.005). The mRNA expression level of ALX-4 in MKN-45 gastric cancer cell line was 2.81±0.07 (P<0.005). We determined that ALX-4 mRNA level significantly correlated with the tumor grade (P=0.004), stage (p=0.000153), but not gender (P= 0.06).

These results documented the important role of ALX-4 in GCSCs, as an oncogene in progressive cancer, and valuable target in the treatment of drug resistant tumors.